Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 62.540
Filtrar
1.
Dev Psychobiol ; 66(5): e22511, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38837722

RESUMO

Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.


Assuntos
Medo , Caracteres Sexuais , Estresse Psicológico , Animais , Medo/fisiologia , Masculino , Feminino , Ratos , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Comportamento Animal/fisiologia , Condicionamento Clássico/fisiologia , Ratos Sprague-Dawley , Hormônios Esteroides Gonadais/metabolismo , Aprendizagem/fisiologia
2.
Minerva Pediatr (Torino) ; 76(3): 343-349, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38842380

RESUMO

BACKGROUND: Previous studies suggested that drawings made by preschool boys and girls show distinguishable differences. However, children's drawings on their own are too complexly determined and inherently ambiguous to be a reliable indicator. In the present study, we attempted to develop a machine learning algorithm for classification of sex of the subjects using children's artworks. METHODS: We studied three types of simple sticker artworks from 1606 Japanese preschool children aged 51-83 months (803 boys and 803 girls). Those artworks were processed into digitalized data. Simulated data based on the original data were also generated. Logistic regression approach was applied to each dataset to make a classifier, and run on each dataset in a stratified ten-fold cross-validation with hyperparameter tuning. A probability score was calculated in each sample and utilized for sex classification. Prediction performance was evaluated using accuracy, recall, and precision scores, as well as learning curves. RESULTS: Two models created from the original and simulated data showed comparably low metrics. The distributions of probability scores in the samples from boys and girls mostly overlapped and were indistinguishable. Learning curves of the models showed an extremely under-fitted pattern. CONCLUSIONS: Our machine learning algorithm was unable to distinguish simple sticker arts created by boys and girls. More complex tasks will enable to develop an accurate classifier.


Assuntos
Aprendizado de Máquina , Humanos , Feminino , Masculino , Pré-Escolar , Criança , Arte , Japão , Algoritmos , Fatores Sexuais , Modelos Logísticos , Caracteres Sexuais
3.
Elife ; 122024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869160

RESUMO

Compared with lowlander migrants, native Tibetans have a higher reproductive success at high altitude though the underlying mechanism remains unclear. Here, we compared the transcriptome and histology of full-term placentas between native Tibetans and Han migrants. We found that the placental trophoblast shows the largest expression divergence between Tibetans and Han, and Tibetans show decreased immune response and endoplasmic reticulum stress. Remarkably, we detected a sex-biased expression divergence, where the male-infant placentas show a greater between-population difference than the female-infant placentas. The umbilical cord plays a key role in the sex-biased expression divergence, which is associated with the higher birth weight of the male newborns of Tibetans. We also identified adaptive histological changes in the male-infant placentas of Tibetans, including larger umbilical artery wall and umbilical artery intima and media, and fewer syncytial knots. These findings provide valuable insights into the sex-biased adaptation of human populations, with significant implications for medical and genetic studies of human reproduction.


Assuntos
Desenvolvimento Fetal , Placenta , Humanos , Feminino , Placenta/metabolismo , Masculino , Gravidez , Desenvolvimento Fetal/genética , Tibet , Recém-Nascido , Transcriptoma , Altitude , Fatores Sexuais , Caracteres Sexuais
4.
Prog Brain Res ; 286: 33-66, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38876578

RESUMO

Verbal short-term and long-term memory are crucial neuropsychological functions involved in core cognitive abilities. They constitute vital components of subjective well-being and academic achievement. To date, there is limited research on the association between regular physical activity and memory abilities during young adulthood. The Individual Alpha Peak Frequency (IAPF) contributes to various cognitive abilities and also appears to be sensitive to physical activity. Consequently, the IAPF has the potential to underlie the association between physical activity and verbal memory. We examined the direct relation of physical activity and verbal memory, and the potential indirect relation via IAPF in young adults. Regular physical activity was assessed via accelerometry on seven consecutive days in 115 participants (N=115, 48% female) aged 18-35 years (M=24.1, SD=3.8). In addition, verbal memory performance was assessed using an immediate and delayed free-recall task. Brain activity during rest was recorded with EEG, and IAPF was extracted for mediation analyses. Path analysis revealed pronounced sex differences in the association between physical activity, IAPF, and verbal memory performance. Exclusively in female participants, higher vigorous physical activity levels were associated with better recall performance. In contrast, no association of physical activity and memory was found in male participants. However, being more physically active was related to a higher IAPF exclusively in male participants. Physical activity shows differential associations between IAPF and verbal memory in male and female participants. However, the lack of a mediating role of IAPF suggests that this neurophysiological marker cannot explain these specific associations in young adults.


Assuntos
Encéfalo , Exercício Físico , Humanos , Feminino , Masculino , Adulto Jovem , Adulto , Adolescente , Exercício Físico/fisiologia , Encéfalo/fisiologia , Eletroencefalografia , Acelerometria , Descanso/fisiologia , Aprendizagem Verbal/fisiologia , Memória/fisiologia , Caracteres Sexuais , Rememoração Mental/fisiologia , Ritmo alfa/fisiologia
5.
Sci Adv ; 10(24): eadi1621, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38865462

RESUMO

The function of germ cells in somatic growth and aging has been demonstrated in invertebrate models but remains unclear in vertebrates. We demonstrated sex-dependent somatic regulation by germ cells in the short-lived vertebrate model Nothobranchius furzeri. In females, germ cell removal shortened life span, decreased estrogen, and increased insulin-like growth factor 1 (IGF-1) signaling. In contrast, germ cell removal in males improved their health with increased vitamin D signaling. Body size increased in both sexes but was caused by different signaling pathways, i.e., IGF-1 and vitamin D in females and males, respectively. Thus, vertebrate germ cells regulate somatic growth and aging through different pathways of the endocrine system, depending on the sex, which may underlie the sexual difference in reproductive strategies.


Assuntos
Envelhecimento , Células Germinativas , Fator de Crescimento Insulin-Like I , Animais , Células Germinativas/metabolismo , Células Germinativas/citologia , Masculino , Feminino , Envelhecimento/fisiologia , Fator de Crescimento Insulin-Like I/metabolismo , Vertebrados , Transdução de Sinais , Caracteres Sexuais , Tamanho Corporal , Vitamina D/metabolismo , Estrogênios/metabolismo
6.
J Neuroinflammation ; 21(1): 151, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840215

RESUMO

BACKGROUND: Mounting evidence links glucose intolerance and diabetes as aspects of metabolic dysregulation that are associated with an increased risk of developing dementia. Inflammation and inflammasome activation have emerged as a potential link between these disparate pathologies. As diet is a key factor in both the development of metabolic disorders and inflammation, we hypothesize that long term changes in dietary factors can influence nervous system function by regulating inflammasome activity and that this phenotype would be sex-dependent, as sex hormones are known to regulate metabolism and immune processes. METHODS: 5-week-old male and female transgenic mice expressing a caspase-1 bioluminescent reporter underwent cranial window surgeries and were fed control (65% complex carbohydrates, 15% fat), high glycemic index (65% carbohydrates from sucrose, 15% fat), or ketogenic (1% complex carbohydrates, 79% fat) diet from 6 to 26 weeks of age. Glucose regulation was assessed with a glucose tolerance test following a 4-h morning fast. Bioluminescence in the brain was quantified using IVIS in vivo imaging. Blood cytokine levels were measured using cytokine bead array. 16S ribosomal RNA gene amplicon sequencing of mouse feces was performed to assess alterations in the gut microbiome. Behavior associated with these dietary changes was also evaluated. RESULTS: The ketogenic diet caused weight gain and glucose intolerance in both male and female mice. In male mice, the high glycemic diet led to increased caspase-1 biosensor activation over the course of the study, while in females the ketogenic diet drove an increase in biosensor activation compared to their respective controls. These changes correlated with an increase in inflammatory cytokines present in the serum of test mice and the emergence of anxiety-like behavior. The microbiome composition differed significantly between diets; however no significant link between diet, glucose tolerance, or caspase-1 signal was established. CONCLUSIONS: Our findings suggest that diet composition, specifically the source and quantity of carbohydrates, has sex-specific effects on inflammasome activation in the central nervous system and behavior. This phenotype manifested as increased anxiety in male mice, and future studies are needed to determine if this phenotype is linked to alterations in microbiome composition.


Assuntos
Caspase 1 , Dieta Cetogênica , Camundongos Transgênicos , Caracteres Sexuais , Animais , Feminino , Masculino , Camundongos , Caspase 1/metabolismo , Dieta Cetogênica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Carboidratos da Dieta/farmacologia , Sistema Nervoso Central/metabolismo , Microbioma Gastrointestinal/fisiologia , Camundongos Endogâmicos C57BL
7.
Sci Data ; 11(1): 586, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839806

RESUMO

Sex bias is known in the prevalence/pathology of neurodevelopmental disorders. Sex-dependent differences of the certain brain areas are known to emerge perinatally through the exposure to sex hormones, while gene expression patterns in the rodent embryonic brain does not seem to be completely the same between male and female. To investigate potential sex differences in gene expression and cortical organization during the embryonic period in mice, we conducted a comprehensive analysis of gene expression for the telencephalon at embryonic day (E) 11.5 (a peak of neural stem cell expansion) and E14.5 (a peak of neurogenesis) using bulk RNA-seq data. As a result, our data showed the existence of notable sex differences in gene expression patterns not obviously at E11.5, but clearly at E14.5 when neurogenesis has become its peak. These data can be useful for exploring potential contribution of genes exhibiting sex differences to the divergence in brain development. Additionally, our data underscore the significance of studying the embryonic period to gain a deeper understanding of sex differences in brain development.


Assuntos
Telencéfalo , Transcriptoma , Animais , Telencéfalo/embriologia , Telencéfalo/metabolismo , Camundongos , Feminino , Masculino , Neurogênese/genética , Caracteres Sexuais
8.
Front Immunol ; 15: 1397579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835755

RESUMO

Background: Yersinia pestis is the etiological agent of plague, which can manifest as bubonic, septicemic, and/or pneumonic disease. Plague is a severe and rapidly progressing illness that can only be successfully treated with antibiotics initiated early after infection. There are no FDA-approved vaccines for plague, and some vaccine candidates may be less effective against pneumonic plague than bubonic plague. Y. pestis is not known to impact males and females differently in mechanisms of pathogenesis or severity of infection. However, one previous study reported sex-biased vaccine effectiveness after intranasal Y. pestis challenge. As part of developing a safe and effective vaccine, it is essential that potential sex differences are characterized. Methods: In this study we evaluated novel vaccines in male and female BALB/c mice using a heterologous prime-boost approach and monitored survival, bacterial load in organs, and immunological correlates. Our vaccine strategy consisted of two subcutaneous immunizations, followed by challenge with aerosolized virulent nonencapsulated Y. pestis. Mice were immunized with a combination of live Y. pestis pgm- pPst-Δcaf1, live Y. pestis pgm- pPst-Δcaf1/ΔyopD, or recombinant F1-V (rF1-V) combined with adjuvants. Results: The most effective vaccine regimen was initial priming with rF1-V, followed by boost with either of the live attenuated strains. However, this and other strategies were more protective in female mice. Males had higher bacterial burden and differing patterns of cytokine expression and serum antibody titers. Male mice did not demonstrate synergy between vaccination and antibiotic treatment as repeatedly observed in female mice. Conclusions: This study provides new knowledge about heterologous vaccine strategies, sex differences in plague-vaccine efficacy, and the immunological factors that differ between male and female mice.


Assuntos
Camundongos Endogâmicos BALB C , Vacina contra a Peste , Peste , Yersinia pestis , Animais , Feminino , Peste/prevenção & controle , Peste/imunologia , Masculino , Yersinia pestis/imunologia , Vacina contra a Peste/imunologia , Vacina contra a Peste/administração & dosagem , Camundongos , Anticorpos Antibacterianos/sangue , Caracteres Sexuais , Fatores Sexuais , Modelos Animais de Doenças , Eficácia de Vacinas
9.
J Neuroinflammation ; 21(1): 150, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840206

RESUMO

Microglia, the brain's resident macrophages, maintain brain homeostasis and respond to injury and infection. During aging they undergo functional changes, but the underlying mechanisms and their contributions to neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia are sex dimorphic, so we compared microglial aging in mice of both sexes. RNA-sequencing of hippocampal microglia revealed more aging-associated changes in female microglia than male microglia, and more sex differences in old microglia than young microglia. Pathway analyses and subsequent validation assays revealed a stronger AKT-mTOR-HIF1α-driven shift to glycolysis among old female microglia and indicated that C3a production and detection was elevated in old microglia, especially in females. Recombinant C3a induced AKT-mTOR-HIF1α signaling and increased the glycolytic and phagocytic activity of young microglia. Single cell analyses attributed the aging-associated sex dimorphism to more abundant disease-associated microglia (DAM) in old female mice than old male mice, and evaluation of an Alzheimer's Disease mouse model revealed that the metabolic and complement changes are also apparent in the context of neurodegenerative disease and are strongest in the neuroprotective DAM2 subset. Collectively, our data implicate autocrine C3a-C3aR signaling in metabolic reprogramming of microglia to neuroprotective DAM during aging, especially in females, and also in Alzheimer's Disease.


Assuntos
Envelhecimento , Microglia , Caracteres Sexuais , Animais , Microglia/metabolismo , Feminino , Camundongos , Envelhecimento/metabolismo , Envelhecimento/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Transdução de Sinais/fisiologia
10.
Brain Behav ; 14(6): e3578, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844426

RESUMO

BACKGROUND: This study aimed to investigate sex differences in risk factors for suicide attempts in first-episode and drug naive (FEDN) major depressive disorder (MDD) with comorbid subclinical hypothyroidism (SCH). METHODS: A total of 1034 FEDN MDD patients with comorbid SCH were enrolled. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess patients' symptoms. Thyroid hormone levels and metabolic parameters were measured. RESULTS: MDD patients with SCH had a significantly higher risk of suicide attempts than those without SCH (25.4% vs. 12.2%). Logistic regression showed that HAMA score, thyroid stimulating hormone (TSH) levels, and thyroid peroxidase antibody (TPOAb) levels were significantly associated with an increased risk for suicide attempts in both male and female MDD patients comorbid SCH, while low-density lipoprotein cholesterol (LDL-C) was significantly associated with an increased risk for suicide attempts only in male patients, HAMD score and systolic blood pressure were significantly associated with an increased risk for suicide attempts only in female patients. CONCLUSION: SCH comorbidities may increase suicide attempts in MDD patients. Our results showed significant sex differences in clinical and metabolic factors associated with suicide attempts among FEDN MDD patients with comorbid SCH, highlighting appropriate sex-based preventive interventions are needed.


Assuntos
Comorbidade , Transtorno Depressivo Maior , Hipotireoidismo , Tentativa de Suicídio , Humanos , Masculino , Feminino , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/sangue , Adulto , Estudos Transversais , Hipotireoidismo/epidemiologia , Hipotireoidismo/sangue , Tentativa de Suicídio/estatística & dados numéricos , China/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , Adulto Jovem , Tireotropina/sangue , População do Leste Asiático
11.
Sci Rep ; 14(1): 12994, 2024 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844574

RESUMO

Women frequently express heightened neck discomfort even though they exhibit smaller neck flexion (NF) during smartphone use. Differences in natural posture while using smartphones may result in varying muscle activation patterns between genders. However, no study focused on this issue. This study investigated the influence of gender on neck muscle activity and NF when using smartphones, ranging from slight (20°) to nearly maximal forward head flexion, across different postures. We analyzed smartphone usage patterns in 16 men and 16 women and examined these behaviors across different scenarios: standing, supported sitting, and unsupported sitting, at 20°, 30°, 40°, and the maximum head angles. During data collection, muscle activity was measured, expressed as a percentage of the maximum voluntary contraction (%MVC), in the cervical erector spinae (CES) and upper trapezius (UTZ), along with NF. Results show significant influences of gender, head angle, and posture on all measures, with notable interactions among these variables. Women displayed higher muscle activities in CES and UTZ, yet exhibited lesser NF, while using smartphones in both standing (12.3%MVC, 10.7% MVC, and 69.0°, respectively) and unsupported sitting (10.8%MVC, 12.3%MVC, and 71.8°, respectively) compared to men (standing: 9.5%MVC, 8.8%MVC, and 76.1°; unsupported sitting: 9.7%MVC, 10.8%MVC, and 76.1°). This study provides a potential rationale for gender-related disparities in injury outcomes, emphasizing that women experience higher neck and shoulder discomfort level, despite their smaller NF during smartphone use, as found in previous research. Additionally, the cervical flexion-relaxation phenomenon may occur when the head angle exceeded 40°. The near-maximum head angle during smartphone use might induce the cervical flexion-relaxation phenomenon, potentially aggravating neck issues. We recommend limiting smartphone usage postures that exceed the near-maximum head angle, as they are commonly adopted by individuals in the daily smartphone activities.


Assuntos
Cabeça , Músculos do Pescoço , Postura , Smartphone , Humanos , Feminino , Masculino , Músculos do Pescoço/fisiologia , Postura/fisiologia , Adulto , Cabeça/fisiologia , Adulto Jovem , Pescoço/fisiologia , Fatores Sexuais , Eletromiografia , Caracteres Sexuais , Cervicalgia/fisiopatologia , Contração Muscular/fisiologia , Amplitude de Movimento Articular/fisiologia
12.
Nat Immunol ; 25(6): 931, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831102
14.
Biol Sex Differ ; 15(1): 47, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844994

RESUMO

BACKGROUND: Sex differences in the brain may play an important role in sex-differential prevalence of neuropsychiatric conditions. METHODS: In order to understand the transcriptional basis of sex differences, we analyzed multiple, large-scale, human postmortem brain RNA-Seq datasets using both within-region and pan-regional frameworks. RESULTS: We find evidence of sex-biased transcription in many autosomal genes, some of which provide evidence for pathways and cell population differences between chromosomally male and female individuals. These analyses also highlight regional differences in the extent of sex-differential gene expression. We observe an increase in specific neuronal transcripts in male brains and an increase in immune and glial function-related transcripts in female brains. Integration with single-nucleus data suggests this corresponds to sex differences in cellular states rather than cell abundance. Integration with case-control gene expression studies suggests a female molecular predisposition towards Alzheimer's disease, a female-biased disease. Autism, a male-biased diagnosis, does not exhibit a male predisposition pattern in our analysis. CONCLUSION: Overall, these analyses highlight mechanisms by which sex differences may interact with sex-biased conditions in the brain. Furthermore, we provide region-specific analyses of sex differences in brain gene expression to enable additional studies at the interface of gene expression and diagnostic differences.


We sought to understand why females have higher rates of Alzheimer's disease, and males have higher rates of autism. One idea was that the female brain at baseline may be more similar to an Alzheimer's brain, so it is easier for them to shift into that state (likewise, males may be more similar to autism). To test this, we examined gene expression differences between brains of biological males and biological females. While all people have the same ~ 25,000 genes, each gene can be on or off ('expressed') to different extents. Overall, we found that there were differences in gene expression between males and females in all brain regions tested but more differences in some brain regions than others. By looking at the role of these genes we estimate that female immune system processes might be more active in the brain. We also found female brain gene expression looked slightly more like people with Alzheimer's compared to people without Alzheimer's, which may explain why females get Alzheimer's disease more easily. However, the male brain gene expression did not look more like autism, suggesting that the reason males have higher rates of autism is complex and needs further investigation.


Assuntos
Doença de Alzheimer , Transtorno Autístico , Encéfalo , Caracteres Sexuais , Humanos , Doença de Alzheimer/genética , Masculino , Feminino , Transtorno Autístico/genética , Encéfalo/metabolismo , Expressão Gênica
15.
Nat Commun ; 15(1): 4893, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849340

RESUMO

Amyotrophic lateral sclerosis (ALS) is a debilitating motor neuron disease and lacks effective disease-modifying treatments. This study utilizes a comprehensive multiomic approach to investigate the early and sex-specific molecular mechanisms underlying ALS. By analyzing the prefrontal cortex of 51 patients with sporadic ALS and 50 control subjects, alongside four transgenic mouse models (C9orf72-, SOD1-, TDP-43-, and FUS-ALS), we have uncovered significant molecular alterations associated with the disease. Here, we show that males exhibit more pronounced changes in molecular pathways compared to females. Our integrated analysis of transcriptomes, (phospho)proteomes, and miRNAomes also identified distinct ALS subclusters in humans, characterized by variations in immune response, extracellular matrix composition, mitochondrial function, and RNA processing. The molecular signatures of human subclusters were reflected in specific mouse models. Our study highlighted the mitogen-activated protein kinase (MAPK) pathway as an early disease mechanism. We further demonstrate that trametinib, a MAPK inhibitor, has potential therapeutic benefits in vitro and in vivo, particularly in females, suggesting a direction for developing targeted ALS treatments.


Assuntos
Esclerose Lateral Amiotrófica , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases , Camundongos Transgênicos , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/metabolismo , Humanos , Feminino , Animais , Masculino , Camundongos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Piridonas/farmacologia , Piridonas/uso terapêutico , Proteína FUS de Ligação a RNA/metabolismo , Proteína FUS de Ligação a RNA/genética , Córtex Pré-Frontal/metabolismo , Transcriptoma , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Pessoa de Meia-Idade , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína C9orf72/genética , Proteína C9orf72/metabolismo , Caracteres Sexuais , Idoso , Fatores Sexuais , Pirimidinonas
16.
J Neuroinflammation ; 21(1): 156, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872143

RESUMO

Repetitive mild traumatic brain injuries (rmTBI) sustained within a window of vulnerability can result in long term cognitive deficits, depression, and eventual neurodegeneration associated with tau pathology, amyloid beta (Aß) plaques, gliosis, and neuronal and functional loss. However, a comprehensive study relating acute changes in immune signaling and glial reactivity to neuronal changes and pathological markers after single and repetitive mTBIs is currently lacking. In the current study, we addressed the question of how repeated injuries affect the brain neuroimmune response in the acute phase of injury (< 24 h) by exposing the 3xTg-AD mouse model of tau and Aß pathology to successive (1x-5x) once-daily weight drop closed-head injuries and quantifying immune markers, pathological markers, and transcriptional profiles at 30 min, 4 h, and 24 h after each injury. We used young adult 2-4 month old 3xTg-AD mice to model the effects of rmTBI in the absence of significant tau and Aß pathology. We identified pronounced sexual dimorphism in this model, with females eliciting more diverse changes after injury compared to males. Specifically, females showed: (1) a single injury caused a decrease in neuron-enriched genes inversely correlated with inflammatory protein expression and an increase in AD-related genes within 24 h, (2) each injury significantly increased a group of cortical cytokines (IL-1α, IL-1ß, IL-2, IL-9, IL-13, IL-17, KC) and MAPK phospho-proteins (phospho-Atf2, phospho-Mek1), several of which co-labeled with neurons and correlated with phospho-tau, and (3) repetitive injury caused increased expression of genes associated with astrocyte reactivity and macrophage-associated immune function. Collectively our data suggest that neurons respond to a single injury within 24 h, while other cell types, including astrocytes, transition to inflammatory phenotypes within days of repetitive injury.


Assuntos
Concussão Encefálica , Camundongos Transgênicos , Animais , Camundongos , Concussão Encefálica/patologia , Concussão Encefálica/imunologia , Concussão Encefálica/metabolismo , Concussão Encefálica/complicações , Feminino , Masculino , Modelos Animais de Doenças , Doença de Alzheimer/patologia , Doença de Alzheimer/imunologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Neuroimunomodulação/fisiologia , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/patologia , Encéfalo/imunologia , Caracteres Sexuais
17.
Biol Sex Differ ; 15(1): 49, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872228

RESUMO

Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males. This observed preponderance of males in autistic populations has served as a focussing framework in all spheres of autism-related issues, from recognition and diagnosis through to theoretical models and research agendas. One related issue is the near total absence of females in key research areas. For example, this paper reports a review of over 120 brain-imaging studies of social brain processes in autism that reveals that nearly 70% only included male participants or minimal numbers (just one or two) of females. Authors of such studies very rarely report that their cohorts are virtually female-free and discuss their findings as though applicable to all autistic individuals. The absence of females can be linked to exclusionary consequences of autism diagnostic procedures, which have mainly been developed on male-only cohorts. There is clear evidence that disproportionately large numbers of females do not meet diagnostic criteria and are then excluded from ongoing autism research. Another issue is a long-standing assumption that the female autism phenotype is broadly equivalent to that of the male autism phenotype. Thus, models derived from male-based studies could be applicable to females. However, it is now emerging that certain patterns of social behaviour may be very different in females. This includes a specific type of social behaviour called camouflaging or masking, linked to attempts to disguise autistic characteristics. With respect to research in the field of sex/gender cognitive neuroscience, there is emerging evidence of female differences in patterns of connectivity and/or activation in the social brain that are at odds with those reported in previous, male-only studies. Decades of research have excluded or overlooked females on the autistic spectrum, resulting in the construction of inaccurate and misleading cognitive neuroscience models, and missed opportunities to explore the brain bases of this highly complex condition. A note of warning needs to be sounded about inferences drawn from past research, but if future research addresses this problem of male bias, then a deeper understanding of autism as a whole, as well as in previously overlooked females, will start to emerge.


Autism is a neurodevelopmental condition, behaviourally identified, which is generally characterised by social communication differences, and restrictive and repetitive patterns of behaviour and interests. It has long been claimed that it is more common in males, with oft-quoted ratios of 4M: 1F. This has been reflected in the development of diagnostic criteria for autism and, consequently, of measures of eligibility for autism research programmes, with females being (as is now emerging) disproportionately excluded.As outlined in this review, this issue has been particularly problematic in brain-based studies of autism. Many studies have only tested male autistic participants, or minimal numbers of autistic females. By default, sex differences were not examined. But the impression given by such research reports has commonly been that the findings would be applicable to all autistic individuals.Recent psychological and clinical research has shown that there are a significant number of autistic females who have been missed by traditional diagnostic practices. Their inclusion has increased their eligibility for autism research studies. With respect to brain research, it has become possible to devise studies with matched numbers of autistic females and males, and to replicate studies that have previously only tested males. Newly emerging findings from such studies are demonstrating that the 'robust' autism-related differences previously observed in autistic male-only cohorts do not fully generalise to autistic females.It will be necessary to exercise caution in drawing inferences from previous male-biased studies of the autistic brain. However, the identification and inclusion of previously excluded female autistic participants hopefully offers more accurate insights into this highly complex and heterogeneous condition.


Assuntos
Transtorno Autístico , Caracteres Sexuais , Humanos , Feminino , Transtorno Autístico/psicologia , Transtorno Autístico/fisiopatologia , Masculino , Neurociência Cognitiva , Encéfalo/fisiopatologia , Comportamento Social , Cognição Social
18.
Sci Rep ; 14(1): 14038, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890406

RESUMO

Face-processing timing differences may underlie visual social attention differences between autistic and non-autistic people, and males and females. This study investigates the timing of the effects of neurotype and sex on face-processing, and their dependence on age. We analysed EEG data during upright and inverted photographs of faces from 492 participants from the Longitudinal European Autism Project (141 neurotypical males, 76 neurotypical females, 202 autistic males, 73 autistic females; age 6-30 years). We detected timings of sex/diagnosis effects on event-related potential amplitudes at the posterior-temporal channel P8 with Bootstrapped Cluster-based Permutation Analysis and conducted Growth Curve Analysis (GCA) to investigate the timecourse and dependence on age of neural signals. The periods of influence of neurotype and sex overlapped but differed in onset (respectively, 260 and 310 ms post-stimulus), with sex effects lasting longer. GCA revealed a smaller and later amplitude peak in autistic female children compared to non-autistic female children; this difference decreased in adolescence and was not significant in adulthood. No age-dependent neurotype difference was significant in males. These findings indicate that sex and neurotype influence longer latency face processing and implicates cognitive rather than perceptual processing. Sex may have more overarching effects than neurotype on configural face processing.


Assuntos
Transtorno Autístico , Encéfalo , Eletroencefalografia , Humanos , Feminino , Masculino , Adolescente , Criança , Adulto , Transtorno Autístico/fisiopatologia , Adulto Jovem , Encéfalo/fisiopatologia , Potenciais Evocados/fisiologia , Reconhecimento Facial/fisiologia , Caracteres Sexuais
19.
Biol Sex Differ ; 15(1): 50, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890702

RESUMO

INTRODUCTION: Active and passive surveillance studies have found that a greater proportion of females report adverse events (AE) following receipt of either the COVID-19 or seasonal influenza vaccine compared to males. In a predominately young adult female population of healthcare workers, we sought to determine the intersection of biological sex and sociocultural gender differences in prospective active reporting of vaccine outcomes, which remains poorly characterized. METHODS: This cohort study enrolled Johns Hopkins Health System healthcare workers (HCWs) who were recruited from the mandatory annual fall 2019-2022 influenza vaccine and the fall 2022 COVID-19 bivalent vaccine campaigns. Vaccine recipients were enrolled the day of vaccination and AE surveys were administered two days post-vaccination for bivalent COVID-19 and influenza vaccine recipients. Data were collected regarding the presence of a series of solicited local and systemic AEs. Open-ended answers about participants' experiences with AEs also were collected for the COVID-19 vaccine recipients. RESULTS: Females were more likely to report local AEs after either influenza (OR = 2.28, p = 0.001) or COVID-19 (OR = 2.57, p = 0.008) vaccination compared to males, regardless of age or race. Males and females had comparable probabilities of reporting systemic AEs after either influenza (OR = 1.18, p = 0.552) or COVID-19 (OR = 0.96, p = 0.907) vaccination. Hormonal birth control use did not impact the rates of reported AEs following influenza vaccination among reproductive-aged female HCWs. Women reported more interruptions in their daily routine following COVID-19 vaccination than men and were more likely to seek out self-treatment. More women than men scheduled their COVID-19 vaccination before their days off in anticipation of AEs. CONCLUSIONS: Our findings highlight the need for sex- and gender-inclusive policies to inform more effective mandatory occupational health vaccination strategies. Further research is needed to evaluate the potential disruption of AEs on occupational responsibilities following mandated vaccination for healthcare workers, a predominately female population, and to more fully characterize the post-vaccination behavioral differences between men and women.


Research that addresses both the sex and gender differences of vaccine outcomes and behaviors is lacking. In this survey study of healthcare workers, comprised of mostly reproductive-aged females/women, we investigated biological sex (male/female) and gender (man/woman) differences in vaccine adverse events and outcomes following either influenza or bivalent COVID-19 vaccination.Regardless of age or race, females were more likely to report local (at injection site), but not systemic (whole body), adverse events than males, consistent across influenza and bivalent COVID-19 vaccine cohorts. Sex hormones are hypothesized to play a role in the differences in immune response following vaccination between males and females. We investigated if hormonal birth control use among females may be associated with differences in vaccine adverse events among the influenza vaccine cohort. However, there was no difference in the likelihood of reporting adverse events between birth control users and non-users. Based on open-ended responses to survey questions, women were found to report more interruptions to their daily routine than men following COVID-19 vaccination. Women were also more likely to seek out self-treatment with over-the-counter medication and intentionally schedule their vaccination around days off in anticipation of adverse events.With nearly 80% of healthcare jobs held by women, even higher for direct patient care positions like nursing, females/women may be disproportionately impacted by mandated annual vaccinations. Vaccinations are necessary for the prevention of disease transmission; however, our findings highlight a need for more equitable occupational vaccine strategies that consider both sex and gender differences.


Assuntos
Vacinas contra COVID-19 , Vacinas contra Influenza , Caracteres Sexuais , Humanos , Feminino , Masculino , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/administração & dosagem , Adulto , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Pessoa de Meia-Idade , Estudos de Coortes , Pessoal de Saúde , Vacinação/efeitos adversos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Influenza Humana/prevenção & controle , Adulto Jovem
20.
Biol Sex Differ ; 15(1): 51, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890762

RESUMO

BACKGROUND: Prenatal alcohol exposure (PAE) can result in lifelong disabilities known as foetal alcohol spectrum disorder (FASD) and is associated with childhood growth deficiencies and increased bone fracture risk. However, the effects of PAE on the adult skeleton remain unclear and any potential sexual dimorphism is undetermined. Therefore, we utilised a murine model to examine sex differences with PAE on in vitro bone formation, and in the juvenile and adult skeleton. METHODS: Pregnant C57BL/6J female mice received 5% ethanol in their drinking water during gestation. Primary calvarial osteoblasts were isolated from neonatal offspring and mineralised bone nodule formation and gene expression assessed. Skeletal phenotyping of 4- and 12-week-old male and female offspring was conducted by micro-computed tomography (µCT), 3-point bending, growth plate analyses, and histology. RESULTS: Osteoblasts from male and female PAE mice displayed reduced bone formation, compared to control (≤ 30%). Vegfa, Vegfb, Bmp6, Tgfbr1, Flt1 and Ahsg were downregulated in PAE male osteoblasts only, whilst Ahsg was upregulated in PAE females. In 12-week-old mice, µCT analysis revealed a sex and exposure interaction across several trabecular bone parameters. PAE was detrimental to the trabecular compartment in male mice compared to control, yet PAE females were unaffected. Both male and female mice had significant reductions in cortical parameters with PAE. Whilst male mice were negatively affected along the tibial length, females were only distally affected. Posterior cortical porosity was increased in PAE females only. Mechanical testing revealed PAE males had significantly reduced bone stiffness compared to controls; maximum load and yield were reduced in both sexes. PAE had no effect on total body weight or tibial bone length in either sex. However, total growth plate width in male PAE mice compared to control was reduced, whilst female PAE mice were unaffected. 4-week-old mice did not display the altered skeletal phenotype with PAE observed in 12-week-old animals. CONCLUSIONS: Evidence herein suggests, for the first time, that PAE exerts divergent sex effects on the skeleton, possibly influenced by underlying sex-specific transcriptional mechanisms of osteoblasts. Establishing these sex differences will support future policies and clinical management of FASD.


Prenatal alcohol exposure (PAE) can lead to a set of lifelong cognitive, behavioural, and physical disabilities known as foetal alcohol spectrum disorder (FASD). FASD is a significant burden on healthcare, justice and education systems, which is set to worsen with rising alcohol consumption rates. FASD children have an increased risk of long bone fracture and adolescents are smaller in stature. However, sex differences and the long-term effects of PAE on the skeleton have not been investigated and was the aim of this study. Using a mouse model of PAE, we examined the function and gene expression of bone-forming cells (osteoblasts). We then analysed the skeletons of male and female mice at 12-weeks-old (adult) and 4-weeks-old (juvenile). PAE reduced osteoblast bone formation in both sexes, compared to control. Differential gene expression was predominantly observed in PAE males and largely involved genes related to blood vessel formation. High resolution x-ray imaging (micro-CT) revealed PAE had a detrimental effect on the inner trabecular bone component in 12-week-old male mice only. Analysis of the outer cortical bone revealed that whilst both male and female PAE mice were negatively affected, anatomical variations were observed. Mechanical testing also revealed differences in bone strength in PAE mice, compared to control. Interestingly, 4-week-old mice did not possess these sex differences observed in our PAE model at 12 weeks of age. Our data suggest PAE has detrimental and yet sex-dependent effects on the skeleton. Establishing these sex differences will support future policies and clinical management of FASD.


Assuntos
Etanol , Camundongos Endogâmicos C57BL , Osteoblastos , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Animais , Feminino , Masculino , Gravidez , Etanol/toxicidade , Etanol/farmacologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Camundongos , Osso e Ossos/efeitos dos fármacos , Microtomografia por Raio-X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...